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We planned a systemic review and meta-analysis to evaluate the diagnostic accuracy of Monocyte Distribution Width (MDW) in aiding the diagnosis of sepsis in the Emergency Department (ED) and Intensive Care Unit (ICU). A systematic literature search was performed in PubMed, Scopus, and OVID to retrieve studies published up to 29 January 2024. We examined results using mean difference and conducted a diagnostic test accuracy (DTA) meta-analysis using a bivariate random effects model. Pooled results showed that MDW was significantly higher in sepsis patients admitted to the ED (MD = 5.59, 95%CI: 4.14–7.05) or to the ICU (MD = 8.30, 95%CI: 2.98–13.62). Nine studies conducted in the ED were included in the DTA review. The overall sensitivity was 0.80 (95%CI: 0.75–0.85), the specificity was 0.76 (95%CI: 0.66–0.83), and the false-positive rate (FPR) was 0.24 (95%CI: 0.17–0.34). Three studies were conducted in the ICU, but only two were included in the DTA meta-analysis. Of the 662 patients admitted to the ICU, 175 developed sepsis, showing higher MDW values than non-septic patients. However, significant heterogeneity was noted among the studies. MDW is a helpful biomarker for sepsis in adult patients admitted to the ED and ICU. In the ED, MDW could aid clinicians in ruling out sepsis.

We carried out a prospective observational study to evaluate whether Monocyte Distribution Width (MDW) may play a role in identifying patients with sepsis in comparison with Procalcitonin (PCT). We prospectively enrolled all consecutive patients hospitalized at the Infectious Diseases Unit of Pescara General Hospital for bacterial infection or sepsis. MDW values were collected for all patients. Clinical characteristics, demographic data, past and present medical history, microbiological results, PCT, as well as neutrophil and monocytes indices at entry were compared in the 2 groups. Two-hundred-sixty patients were enrolled, 63.5% males, aged 59.1±19.5 years. Sepsis was diagnosed in 105 (40.4%); in 60 (57.1%) at least 1 microorganism was isolated from blood cultures. In multivariate models, MDW as a continuous variable (OR:1.57 for each unit increase; 95%CI: 1.31-1.87, p<0.001) and PCT˃1 ng/mL (OR: 48.5; 95%CI: 14.7-160.1, p<0.001) were independently associated with sepsis. Statistical best cut points associated with sepsis were 22.0 for MDW and 1.0 ng/mL for PCT whereas MDW values<20 were invariably associated with negative blood cultures. At ROC curve analysis, the AUC of MDW (0.87) was nearly overlapping that of PCT (0.88). Our data suggest that incorporating MDW within current routine WBC counts and indices may be of remarkable use for detection of sepsis. Further research is warranted.

Background Early recognition of patients hospitalized for sepsis at higher risk of poor clinical outcome is a mandatory task and many studies suggested that indicators of the immune status may be useful for this purpose. We performed a retrospective, monocentric cohort study to evaluate whether lymphocyte subsets may be useful in predicting in-hospital mortality of septic patients. Methods Data of all consecutive patients with a diagnosis of sepsis at discharge and an available peripherical blood lymphocyte subset (CD4, CD8, CD16/CD56 and CD19) analysis at hospital entry were retrospectively collected between January 2015 and August 2018. Clinical characteristics of patients, past medical history and other laboratory parameters were also considered. Results Two-hundred-seventy-eight septic patients, 171 (61.5%) males, mean age 63.2 ± 19.6 years, were enrolled. Total counts of lymphocytes, CD4 T cells, CD8 T cells and B cells were found significantly lower in deceased than in surviving patients. At univariate analyses, CD4 T cells/µL (OR 0.99 for each incremental unit, 95%CI 0.99–1.10, p < 0.0001), age (OR 1.06, 95%CI 1.04–1.09, p < 0.0001), procalcitonin (OR 1.01, 95%CI 1.01–1.02, p < 0.0001) and female gender (OR 2.81, 95%CI 1.49–5.28, p = 0.001) were associated with in-hospital mortality. When a dichotomic threshold of < 400/µL for CD4 T cells as a dependent variable was considered in multivariate models, age (OR 1.04; 95%CI 1.01–1.09, p = 0.018); female gender (OR 3.18; 95%CI 1.40–7.20, p = 0.006), qSOFA (OR 4.00, 95%CI 1.84–8.67, p < 0.001) and CD4 T cells < 400/µL (OR 5.3; 95%CI 1.65–17.00, p = 0.005) were the independent predictors. Conclusions In adjunct to biomarkers routinely determined for the prediction of prognosis in sepsis, CD4 T lymphocytes, measured at hospital entry, may be useful in identifying patients at higher risk of in-hospital death.

Background Monocyte Distribution Width (MDW), a simple proxy marker of innate monocyte activation, can be used for the early recognition of sepsis along with Procalcitonin. This study explored the added value of MDW as an early predictor of ensuing sepsis in patients hospitalised in an Intensive Care Unit. Methods We performed an observational prospective monocentric study to estimate the analytical performance of MDW in detecting ensuing sepsis in a sample of consecutive patients assisted in an Intensive Care Unit for > 48 h for any reason. Demographic and clinical characteristics, past medical history and other laboratory measurements were included as potential predictors of confirmed sepsis in multivariate logistic regression. Results A total of 211 patients were observed, 129 of whom were included in the final sample due to the suspect of ensuing sepsis; of these, 74 (57%) had a confirmed diagnosis of sepsis, which was best predicted with the combination of MDW > 23.0 and PCT > 0.5 ng/mL (Positive Predictive Value, PPV: 92.6, 95% CI: 82.1–97.9). The best MDW cut-off to rule out sepsis was ≤20.0 (Negative Predictive Value, NPV: 86.4, 95% CI: 65.1–97.1). Multivariate analyses using both MDW and PCT found a significant association for MDW > 23 only (OR:17.64, 95% CI: 5.53–67.91). Conclusion We found that values of MDW > 23 were associated with a high PPV for sepsis, whereas values of MDW ≤ 20 were associated with a high NPV. Our findings suggest that MDW may help clinicians to monitor ICU patients at risk of sepsis, with minimal additional efforts over standard of care.

Background Monocyte Distribution Width (MDW), a simple cellular marker of innate monocyte activation, can be used for the early recognition of sepsis. We performed an observational prospective monocentric study to assess the predictive role of MDW in detecting sepsis in a sample of consecutive patients presenting at the Emergency Department. Methods Prospective observational study using demographic and clinical characteristics, past medical history and other laboratory measurements to predict confirmed sepsis using multivariate logistic regression. Results A total of 2724 patients were included in the study, of which 272 (10%) had sepsis or septic shock. After adjusting for known and potential risk factors, logistic regression found the following independent predictors of sepsis: SIRS equal to 1 (OR: 2.32, 1.16–4.89) and 2 or more (OR: 27.8, 14.8–56.4), MDW > 22 (OR: 3.73, 2.46–5.70), smoking (OR: 3.0, 1.22–7.31), end stage renal function (OR: 2.3, 1.25–4.22), neurodegenerative disease (OR: 2.2, 1.31–3.68), Neutrophils ≥ 8.9 × 10 3 /µL (OR: 2.73, 1.82–4.11), Lymphocytes < 1.3 × 10 3 /µL (OR: 1.72, 1.17–2.53) and CRP ≥ 19.1 mg/L (OR: 2.57, 1.63–4.08). A risk score derived from predictive models achieved high accuracy by using an optimal threshold (AUC: 95%; 93–97%). Conclusions The study suggests that incorporating MDW in the clinical decision process may improve the early identification of sepsis, with minimal additional effort on the standard procedures adopted during emergency care.

Background The hospital management of patients diagnosed with COVID-19 can be hampered by heterogeneous characteristics at entry into the emergency department. We aimed to identify demographic, clinical and laboratory parameters associated with higher risks of hospitalisation, oxygen support, admission to intensive care and death, to build a risk score for clinical decision making at presentation to the emergency department. Methods We carried out a retrospective study using linked administrative data and laboratory parameters available in the initial phase of the pandemic at the emergency department of the regional reference hospital of Pescara, Abruzzo, Italy, March–June 2020. Logistic regression and Cox modelling were used to identify independent predictors for risk stratification. Validation was carried out collecting data from an extended timeframe covering other variants of concern, including Alpha (December 2020–January 2021) and Delta/Omicron (January–March 2022). Results Several clinical and laboratory parameters were significantly associated to the outcomes of interest, independently from age and gender. The strongest predictors were: for hospitalisation, monocyte distribution width ≥ 22 (4.09; 2.21–7.72) and diabetes (OR = 3.04; 1.09–9.84); for oxygen support: saturation < 95% (OR = 11.01; 3.75–41.14), lactate dehydrogenase≥237 U/L (OR = 5.93; 2.40–15.39) and lymphocytes< 1.2 × 10 3 /μL (OR = 4.49; 1.84–11.53); for intensive care, end stage renal disease (OR = 59.42; 2.43–2230.60), lactate dehydrogenase≥334 U/L (OR = 5.59; 2.46–13.84), D-dimer≥2.37 mg/L (OR = 5.18; 1.14–26.36), monocyte distribution width ≥ 25 (OR = 3.32; 1.39–8.50); for death, procalcitonin≥0.2 ng/mL (HR = 2.86; 1.95–4.19) and saturation < 96% (HR = 2.74; 1.76–4.28). Risk scores derived from predictive models using optimal thresholds achieved values of the area under the curve between 81 and 91%. Validation of the scoring algorithm for the evolving virus achieved accuracy between 65 and 84%. Conclusions A set of parameters that are normally available at emergency departments of any hospital can be used to stratify patients with COVID-19 at risk of severe conditions. The method shall be calibrated to support timely clinical decision during the first hours of admission with different variants of concern.

Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11–2.02), SAPS II (OR: 1.05, CI: 1.01–1.1), SOFA score (OR: 1.37, CI: 1.06–1.76), lymphocytopenia (OR: 32.5, CI: 3.45–306.4), viral reactivation (OR: 9.75, CI: 1.72–55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8–271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98–2.05), lymphocytopenia (OR: 18.2, CI: 0.87–371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77–123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients’ care.

Background We investigated the possible role of the immune profile at ICU admission, among other well characterized clinical and laboratory predictors of unfavorable outcome in COVID-19 patients assisted in ICU. Methods Retrospective analysis of clinical and laboratory data collected for all consecutive patients admitted to the ICUs of the General Hospital of Pescara (Abruzzo, Italy), between 1 st March 2020 and 30 th April 2021, with a confirmed diagnosis of COVID-19 respiratory failure. Logistic regressions were used to identify independent predictors of bacteremia and mortality. Results Out of 431 patients included in the study, bacteremia was present in N  = 191 (44.3%) and death occurred in N  = 210 (48.7%). After multivariate analysis, increased risk of bacteremia was found for viral reactivation (OR = 3.28; 95% CI:1.83–6.08), pronation (3.36; 2.12–5.37) and orotracheal intubation (2.51; 1.58–4.02). Increased mortality was found for bacteremia (2.05; 1.31–3.22), viral reactivation (2.29; 1.29–4.19) and lymphocytes < 0.6 × 10 3 c/µL (2.32; 1.49–3.64). Conclusions We found that viral reactivation, mostly due to Herpesviridae, was associated with increased risk of both bacteremia and mortality. In addition, pronation and intubation are strong predictors of bacteremia, which in turn together with severe lymphocytopenia due to SARS-CoV2 was associated with increased mortality. Most episodes of bacteremia, even due to Acinetobacter spp, were not predicted by microbiological evidence of colonization.

Background: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions. Methods: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist. Results: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%–1.4%,) and 6.5% (95% CI: 4.7–8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5–54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%. Conclusions: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.

Background The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn’s Disease (CD) with ensuing neurological symptoms. Case presentation A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn’s Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure. Conclusions Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.